High-performance cloud computing (HPCC) integrates high-performance computing (HPC) with cloud computing to provide the supercomputing informatics infrastructure needed for the processing and mobile display of high quality, multi-dimensional diagnostic images. Such infrastructure would advance high-throughput cancer screening like virtual colonoscopy (VC), also known as computed tomography colonography (CTC). The short-term goals of this proposal are to develop and validate the clinical benefits of a novel mobile next-generation HPCC-VC decision support system (HPCC-VC2) that integrates (1) a high-performance iterative reconstruction techniques (hpIRT) for reconstructing ultra-low-dose (ULD) super-resolution (SR) multi-energy laxative-free CTC (ME-lfCTC) images, (2) a high-performance computer-assisted bowel preparation (hpCABP) scheme for removal of residual fecal materials and a high-performance computer-aided detection (hpCADe) scheme and detection of polypoid and flat non-polypoid lesions in ME-lfCTC. Specifically, we hypothesize that the HPCC-VC2 system will (1) provide an ME-lfCTC examination at an ULD of 1 mSy or less, (2) achieve high detection performance for colorectal lesions, (3) prepare a CTC examination within 5 minutes, and (4) improve readers' performance in the detection of colorectal lesions from lfCTC images shown on mobile display devices. The specific aims are: (1) develop dynamic compression scheme for rapid uploading of raw CTC data to the HPCC; (2) develop parallel hpIRT method for ULD SR ME-CTC; (3) develop parallel hpCABP and hpCADe schemes for the HPCC-VC2; and (4) evaluate the clinical benefit of the HPCC-VC2 system. Successful development of the HPCC-VC2 system will demonstrate the clinical benefit of the platform for improved diagnostic imaging and facilitation of accurate, high-throughput colon cancer screening that is highly acceptable to patients. In the longer term, broad adoption and use of the HPCC-VC2 system will facilitate early and accurate diagnoses, and thus will reduce mortality from colon cancer that is currently the third leading cause of cancer deaths in the United States.